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Definition of encephalitogenic and immunodominant epitopes of guinea pig myelin basic protein (Gp-BP) in Lewis rats tolerized neonatally with Gp-BP or Gp-BP peptides.
J Immunol. 1994 Jul 15; 153(2):852-61.JI

Abstract

Two distinct epitopes of guinea pig basic protein (Gp-BP), residues 72-89 and 87-99, possess encephalitogenic activity in Lewis rats. The purpose of this study was to determine to what degree the 87-99 epitope functions in rats that have been injected with whole Gp-BP, and whether additional epitopes in Gp-BP are encephalitogenic. To address these questions, we induced neonatal tolerance to the dominant synthetic (S)72-89 peptide or to the combination of both S72-89 and S87-99 peptides, and evaluated resistance to experimental autoimmune encephalomyelitis (EAE) induced by Gp-BP, as well as T cell responses to peptides that encompassed most of the Gp-BP molecule. The results demonstrated that virtually all of the encephalitogenic activity of Gp-BP resides within the two described encephalitogenic epitopes. Moreover, deletion of responses to the dominant epitopes prompted T cell responses to other nonencephalitogenic epitopes of Gp-BP, a pattern of response observed previously in rats that had recovered from EAE and in those protected from EAE by vaccination with TCR peptides. These data may have relevance to human autoimmune diseases such as multiple sclerosis in that naturally or immunologically regulated responses to dominant epitopes that are likely to be encephalitogenic may be obscured by increased responses to relatively innocuous determinants of basic protein. Elevated responses to potentially pathogenic autoantigens will likely involve both types of determinants, thus, underscoring the importance of distinguishing encephalitogenic from nonencephalitogenic determinants.

Authors+Show Affiliations

Veterans Affairs Medical Center, Portland, OR 97201.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7517426

Citation

Vandenbark, A A., et al. "Definition of Encephalitogenic and Immunodominant Epitopes of Guinea Pig Myelin Basic Protein (Gp-BP) in Lewis Rats Tolerized Neonatally With Gp-BP or Gp-BP Peptides." Journal of Immunology (Baltimore, Md. : 1950), vol. 153, no. 2, 1994, pp. 852-61.
Vandenbark AA, Vainiene M, Celnik B, et al. Definition of encephalitogenic and immunodominant epitopes of guinea pig myelin basic protein (Gp-BP) in Lewis rats tolerized neonatally with Gp-BP or Gp-BP peptides. J Immunol. 1994;153(2):852-61.
Vandenbark, A. A., Vainiene, M., Celnik, B., Hashim, G. A., Buenafe, A., & Offner, H. (1994). Definition of encephalitogenic and immunodominant epitopes of guinea pig myelin basic protein (Gp-BP) in Lewis rats tolerized neonatally with Gp-BP or Gp-BP peptides. Journal of Immunology (Baltimore, Md. : 1950), 153(2), 852-61.
Vandenbark AA, et al. Definition of Encephalitogenic and Immunodominant Epitopes of Guinea Pig Myelin Basic Protein (Gp-BP) in Lewis Rats Tolerized Neonatally With Gp-BP or Gp-BP Peptides. J Immunol. 1994 Jul 15;153(2):852-61. PubMed PMID: 7517426.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Definition of encephalitogenic and immunodominant epitopes of guinea pig myelin basic protein (Gp-BP) in Lewis rats tolerized neonatally with Gp-BP or Gp-BP peptides. AU - Vandenbark,A A, AU - Vainiene,M, AU - Celnik,B, AU - Hashim,G A, AU - Buenafe,A, AU - Offner,H, PY - 1994/7/15/pubmed PY - 1994/7/15/medline PY - 1994/7/15/entrez SP - 852 EP - 61 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 153 IS - 2 N2 - Two distinct epitopes of guinea pig basic protein (Gp-BP), residues 72-89 and 87-99, possess encephalitogenic activity in Lewis rats. The purpose of this study was to determine to what degree the 87-99 epitope functions in rats that have been injected with whole Gp-BP, and whether additional epitopes in Gp-BP are encephalitogenic. To address these questions, we induced neonatal tolerance to the dominant synthetic (S)72-89 peptide or to the combination of both S72-89 and S87-99 peptides, and evaluated resistance to experimental autoimmune encephalomyelitis (EAE) induced by Gp-BP, as well as T cell responses to peptides that encompassed most of the Gp-BP molecule. The results demonstrated that virtually all of the encephalitogenic activity of Gp-BP resides within the two described encephalitogenic epitopes. Moreover, deletion of responses to the dominant epitopes prompted T cell responses to other nonencephalitogenic epitopes of Gp-BP, a pattern of response observed previously in rats that had recovered from EAE and in those protected from EAE by vaccination with TCR peptides. These data may have relevance to human autoimmune diseases such as multiple sclerosis in that naturally or immunologically regulated responses to dominant epitopes that are likely to be encephalitogenic may be obscured by increased responses to relatively innocuous determinants of basic protein. Elevated responses to potentially pathogenic autoantigens will likely involve both types of determinants, thus, underscoring the importance of distinguishing encephalitogenic from nonencephalitogenic determinants. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7517426/Definition_of_encephalitogenic_and_immunodominant_epitopes_of_guinea_pig_myelin_basic_protein__Gp_BP__in_Lewis_rats_tolerized_neonatally_with_Gp_BP_or_Gp_BP_peptides_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=7517426 DB - PRIME DP - Unbound Medicine ER -